POS0382 PHYSICAL ACTIVITY, SEDENTARY TIME AND INFLAMMATORY BOWEL DISEASES RISK: A MENDELIAN RANDOMIZATION STUDY
Authors: Y. Zhao, H. LI, L. Jia, M. J. Chang, S. X. Zhang, Q. Yu, P. F. He
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Inflammatory bowel disease (IBD) is a chronic and recurring intestinal inflammatory disease, that includes Crohn’s disease (CD) and ulcerative colitis (UC). There is no known cure for IBD and its subtypes. It is essential to identify modifiable risk factors and seek potential treatments to slow down the progression or even prevent the onset of these diseases. As one of these factors, physical activity and sedentary time have recently aroused much research interest in the coming years. However, previous observational studies designed to examine the relationship between physical activity, sedentary time and inflammatory bowel diseases have mostly yielded inconsistent results. Furthermore, whether observed associations are causal remains elusive due to reverse causation and residual confounding noted in observational studies. <h3>Objectives</h3> Mendelian randomization (MR) assesses causality by using genotypes to simulate randomized trial groups. Herein, we assessed whether lifelong physical activity (i.e., moderate to vigorous intense physical activity [MVPA]) or sedentary time (sedentary behavior at work, sedentary commuting, and leisure screen time [LST]) has the potential causal relationship with the risk for IBD and its subtypes, using a genetically informed method. <h3>Methods</h3> Instrumental variables (IVs) for the main exposures in our study were extracted from the latest published meta-analysis of up to 703,901 European individuals in 51 studies on a genome-wide-association study (GWAS) for self-reported MVPA, LST, sedentary commuting, and sedentary behavior at work (minimum n = 159,606; maximum n = 608,595)<sup>[1]</sup>. Summary statistics for IBD, CD, and UC were retrieved from the up-to-date studies in European ancestry (cases/controls for IBD: 25042/34915; CD: 12194/28072; UC: 12366/33609)<sup>[2]</sup>. The inverse variance weighted (IVW) method was utilized as the primary MR analysis. Weighted median and MR-Egger were then implemented as complements to the IVW. <h3>Results</h3> Mendelian randomization evidence suggested a protective relationship between MVPA and IBD (Figure 1a) (IBD: odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.47 to 0.95, P = 0.03) and CD (Figure 1b) (OR: 0.53, 95% CI: 0.30 to 0.94, P = 0.03). Greater genetically-predicted LST was associated with higher risks of IBD (Figure 1c) (IBD: OR: 1.21, 95% CI: 1.06 to 1.38, P = 0.004) and CD (Figure 1d) (OR: 1.25, 95% CI: 1.07 to 1.45, P = 0.004). In contrast, there was no statistically significant relationship between MVPA and UC (OR: 0.76, 95% CI: 0.49 to 1.18, P = 0.23). A similar insignificant association was found between LST and UC (OR: 1.12, 95% CI: 0.95 to 1.32, P = 0.18). Furthermore, there was no significant relationship between sedentary behavior at work and IBD (including CD and UC) or between sedentary commuting and IBD (including CD and UC) with a P-value &gt; 0.05. <h3>Conclusion</h3> Our study provides strong evidence that greater MVPA and lower LST are likely to reduce the risks for IBD and CD. Particular attention should be given to reducing LST and encouraging proper physical activities during the management and treatment of IBD and CD. <h3>References</h3> [1]Wang Z, Emmerich A, Pillon NJ, et al. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention. Nat Genet 2022;54(9):1332-44. [2]de Lange KM, Moutsianas L, Lee JC, et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 2017;49(2):256-61. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.